Development and Validation of Prognostic Nomograms Predicting Recurrence and Survival in Patients with Solitary Hepatocellular Carcinoma Following Curative Liver Resection

Author(s):  
Xinxin Chen ◽  
Wenxia Qiu ◽  
Xuekun Xie ◽  
Zefeng Chen ◽  
Zhiwei Han ◽  
...  

Abstract Background: This work was designed to establish and verify our nomograms integrating clinicopathological characteristics with hematological biomarkers to predict both disease-free survival (DFS) and overall survival (OS) in solitary hepatocellular carcinoma (HCC) patients following hepatectomy.Methods: We scrutinized the data retrospectively from 414 patients with a clinicopathological diagnosis of solitary HCC from Guangxi Medical University Cancer Hospital (Nanning, China) between January 2004 and December 2012. Following the random separation of the samples in a 7:3 ratio into the training set and validation set, the former set was assessed by Cox regression analysis to develop two nomograms to predict the 1-year and 3-year DFS and OS (3-years and 5-years). This was followed by discrimination and calibration estimation employing Harrell’s C-index (C-index) and calibration curves, while the internal validation was also assessed.Results: In the training cohort, the tumor diameter, tumor capsule, macrovascular invasion, and alpha-fetoprotein (AFP) were included in the DFS nomogram. Age, tumor diameter, tumor capsule, macrovascular invasion, microvascular invasion, and aspartate aminotransferase (AST) were included in the OS nomogram. The C-index was 0.691 (95% CI: 0.644-0.738) for the DFS-nomogram and 0.713 (95% CI: 0.670-0.756) for the OS-nomogram. The survival probability calibration curves displayed a fine agreement between the predicted and observed ranges in both data sets. Conclusion: Our nomograms combined clinicopathological features with hematological biomarkers to emerge effective in predicting the DFS and OS in solitary HCC patients following curative liver resection. Therefore, the potential utility of our nomograms for guiding individualized treatment clinically and monitor the recurrence monitoring in these patients.

2021 ◽  
Author(s):  
Youya Zang ◽  
Peiyun Long ◽  
Ming Wang ◽  
Shan Huang ◽  
Chuang Chen

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The existing staging system has a limited budget capacity for HCC recurrence. The authors aimed to establish and verify two nomogram models to predict disease-free survival (DFS) and overall survival (OS) in patients with HCC. Methods: Patients diagnosed with HCC between August 2011 and March 2016 were recruited. Data were randomly divided into a training cohort and a validation cohort. Based on univariate and multivariate Cox regression analysis, independent risk factors for DFS and OS were identified, and two nomogram models were established to predict patient survival. Results: Sex, tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, tumor capsule, macrovascular invasion, AST-to-platelet ratio index, AST-to-lymphocyte ratio index, neutrophil–lymphocyte ratio and alpha-fetoprotein (AFP) were used to build the nomogram for DFS, while age, tumor size, BCLC stage, tumor capsule, macrovascular invasion, systemic immune-inflammation index, AST, total bilirubin and AFP were used to build the nomogram for OS. Calibration curves showed good agreement between the nomogram prediction and actual observation. C-indices in both nomograms were significantly higher than BCLC. Conclusion: The two nomograms improved the accuracy of individualized prediction of DFS and OS, which may help doctors screen patients with a high risk of recurrence to formulate individualized treatment plans.


2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Feng Tian ◽  
Jian Xu ◽  
Fangxi Xue ◽  
Encui Guan ◽  
Xiaoguang Xu

Emerging evidence are accumulating that long noncoding RNAs (lncRNAs) have recently been identified to participate in various cellular processes. Terminal differentiation induced ncRNA (TINCR) is a newly identified lncRNA with its functional roles not fully elucidated in human malignancy. The current study aims to identify the clinical significance of TINCR in prognosis and malignant progression of hepatocellular carcinoma (HCC). TINCR expression in HCC specimens at various stages of tumorigenesis were measured by quantitative real-time RT PCR (qRT-PCR). The matched para-carcinoma tissues were used as controls. The associations of TINCR with clinicopathological characteristics, disease-free survival (DFS) and overall survival (OS) of patients were further evaluated. Results revealed that high TINCR expression was significantly correlated with tumor size (P=0.005), tumor differentiation status (P=0.017), TNM stage (P=0.010), and vascular invasion (P=0.004). Moreover, Kaplan–Meier analysis demonstrated that TINCR was correlated to both DFS and OS in HCC cohorts. Patients with high TINCR expression tended to have worse prognosis. Multivariate Cox regression analysis indicated that TINCR was an independent poor prognostic indicator for DFS (HR =1.32, 95% CI: 1.00–1.57, P=0.000) and OS (HR =1.57, 95% CI: 1.30–1.86, P=0.004) in HCC. TINCR was demonstrated as a direct target of miR-137 and miR-133a, and was suppressed by miR-137/miR-133a. These results provide the first evidence that the expression of TINCR in HCC may play an oncogenic role in HCC differentiation, invasion, and metastasis. miR-137/miR-133a-TINCR pathway may serve as a promising target for tumor recurrence and prognosis of patients with HCC.


2021 ◽  
Author(s):  
hu panyi ◽  
Yongwei Zhang ◽  
yeben qian

Abstract Background: Objective to evaluate the predictive value of preoperative fibrinogen and systemic inflammatory response index (F-SIRI) in the prognosis of patients with hepatocellular carcinoma after radical hepatectomy. Methods: the clinical data of 298 patients with hepatocellular carcinoma who underwent surgery and confirmed by postoperative pathology in our hospital from January 2015 to December 2017 were retrospectively analyzed. The F-SIRI score was calculated according to FIB and SIRI data of peripheral blood. The relationship between F-SIRI score and clinicopathological characteristics was analyzed. The survival analysis was performed by Kaplan Meier method, Cox regression analysis was used to analyze the prognostic factors. Results: preoperative F-SIRI score was correlated with tumor diameter, FIB and SIRI (P<0.05), but not with age, gender, TNM stage and other clinical features (P>0.05). There were significant differences in the 5-year DFS rate and OS rate among patients with different preoperative F-SIRI scores(P<0.05); Cox regression analysis showed that preoperative tumor diameter, alpha fetoprotein level and F-SIRI score were independent predictors of DFS in patients with HCC (P< 0.05), while preoperative tumor diameter, ALB and F-SIRI score as independent predictors of OS (P<0.05). Conclusion: preoperative F-SIRI is an independent prognostic factor in patients with HCC after radical hepatectomy, with poor prognosis in patients with high level of F-SIRI.


2021 ◽  
Author(s):  
Daw-Shyong Perng ◽  
Hung-Yu Lin ◽  
Paul Morgan ◽  
Tsung-Chin Wu ◽  
Chao-Ming Hung ◽  
...  

Abstract Background: Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). Methods: We prospectively investigated how these proteins affect clinical prognosis in 40 patients who underwent hepatectomy for cHCC-CC from 2011 to 2019 at a Taiwanese hospital. Levels of autophagy-related proteins, namely LC3, Beclin-1, and p62, were immunohistochemically assessed in patient tumor and non-tumor tissues. Results: We noted that LC3 expression was significantly correlated with mild clinicopathological characteristics, including macrovascular invasion, lymph node metastasis, American Joint Committee on Cancer and Barcelona Clinic Liver Cancer stages, recurrence, and mortality. Ten patient showed tumor recurrence, and 15 patients died. Postresection 5-year OS and DFS rates were 43.7% and 57.4%, respectively. Cox regression analysis showed that high intratumoral LC3 expression was significantly associated with improved OS [hazard ratio (HR; 95% confidence interval (CI)): (1.68–26.9), p = 0.007], but multiple tumors and microvascular invasion was significantly correlated with poor OS [HR (95% CI): 0.03 (0.01–0.34), p = 0.004, and 0.07 (0.01–0.46), p = 0.006, respectively]. Furthermore, high LC3 expression and cirrhosis had improved DFS [HR (95% CI): 51.3 (2.85–922), p = 0.008, and 17.9 (1.05–306), p = 0.046, respectively]. The 5-year OS and DFS rates were respectively 61.2% and 74.6% in high LC3 expression patients and 0% and 0% in those with low LC3 expression. Conclusion: High LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Daw-Shyong Perng ◽  
Chao-Ming Hung ◽  
Hung-Yu Lin ◽  
Paul Morgan ◽  
Yao-Chun Hsu ◽  
...  

Abstract Background Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). Methods We prospectively investigated how these proteins affect clinical prognosis in 40 patients who underwent hepatectomy for cHCC-CC from 2011 to 2019 at a Taiwanese hospital. Levels of autophagy-related proteins, namely LC3, Beclin-1, and p62, were immunohistochemically assessed in patient tumor and non-tumor tissues. Results We noted that LC3 expression was significantly correlated with mild clinicopathological characteristics, including macrovascular invasion, lymph node metastasis, American Joint Committee on Cancer and Barcelona Clinic Liver Cancer stages, recurrence, and mortality. Ten patient showed tumor recurrence, and 15 patients died. Postresection 5-year OS and DFS rates were 43.7 and 57.4%, respectively. Cox regression analysis showed that high intratumoral LC3 expression was significantly associated with improved OS [hazard ratio (HR; 95% confidence interval (CI)): (1.68–26.9), p = 0.007], but multiple tumors and microvascular invasion was significantly correlated with poor OS [HR (95% CI): 0.03 (0.01–0.34), p = 0.004, and 0.07 (0.01–0.46), p = 0.006, respectively]. Furthermore, high LC3 expression and cirrhosis had improved DFS [HR (95% CI): 51.3 (2.85–922), p = 0.008, and 17.9 (1.05–306), p = 0.046, respectively]. The 5-year OS and DFS rates were respectively 61.2 and 74.6% in high LC3 expression patients and 0 and 0% in those with low LC3 expression. Conclusion High LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.


2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Ji-sheng Jing ◽  
Hongbo Li ◽  
Shun-cai Wang ◽  
Jiu-ming Ma ◽  
La-qing Yu ◽  
...  

N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan–Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan–Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.


2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Sanshun Zhou ◽  
Zusen Wang ◽  
Manjiang Li ◽  
Liqun Wu

Aim. Little is known about the association between cancer antigen 125 (MUC16/CA125) concentrations and tumor diameter of patients with hepatocellular carcinoma (HCC) and low AFP levels. To fill this gap in our knowledge, we conducted a retrospective study of 427 patients with HCC with AFP ≤200 ng/mL who underwent R0 resection at our center. Methods. The associations between CA125 concentrations and patients’ clinicopathological characteristics were analyzed. Survival vs CA125 levels was also evaluated between patient groups with CA125 ≤30 U/mL or CA125 >30 U/mL. Independent risk factors of disease-free survival (DFS) and overall survival (OS) were analyzed with Cox hazard regression model. Results. Elevated preoperative serum CA125 was significantly associated with maximal tumor diameter (MTD) >5 cm and female sex (P<0.001 and P=0.044, respectively). The DFS and OS of patients with CA125 ≤30 U/mL (n = 392) were significantly higher compared with those with CA125 >30 U/mL (n = 35) (P=0.003 and P=0.001 respectively). Multivariate analysis revealed that MTD >5 cm was an independent risk factor of DFS (HR = 1.891, 95% CI: 1.379–2.592, P<0.001) and OS (2.709, 1.848–3.972, P<0.001). Conclusions. In conclusion, elevated preoperative serum CA125 predicted larger tumor diameter and poor prognosis after patients with HCC with AFP ≤200 ng/mL underwent R0 resection, which may be explained by the elevation of the preoperative serum CA125 level significantly associated with MTD>5 cm.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17130-e17130 ◽  
Author(s):  
Rüdiger Klapdor ◽  
Peter Hillemanns ◽  
Linn Lena Woelber ◽  
Julia Kathrin Jueckstock ◽  
Felix Hilpert ◽  
...  

e17130 Background: Obesity is associated with worse patients’ survival in several cancer entities. Vulvar cancer as well as obesity show increasing incidence over the last years. The influence of obesity on prognosis of vulvar cancer patients is not clear. However, knowledge about this may have consequences on prevention, treatment, and follow-up. Methods: This is an analysis of the large AGO-CaRE-1 study. Patients suffering from squamous cell vulvar cancer (UICC stage IB and higher), treated in 29 cancer centers between 1998 and 2008, were categorized in a database, in order to analyze treatment patterns and prognostic factors in a retrospective setting. Results: In total, 849 patients with documented height and weight were divided into two groups depending on their body mass index (BMI, < 30 vs. ≥30 kg/m²). There was no difference in the baseline variables (age, tumor diameter, depth of infiltration, tumor stage, nodal invasion, tumor grade) between both groups (p > 0.05). However, we identified differences regarding ECOG status and preexistent comorbidities (cardiovascular, dementia) towards healthier patients with BMI < 30 kg/m². Treatment variables (R0 resection, chemotherapy, radiotherapy, continuation of adjuvant therapy) did not differ (p > 0.05). Patients with BMI ≥30 kg/m² underwent radical vulvectomy more often (61.1 % vs. 51.8%, p = 0.042). During follow-up, there was a higher recurrence rate in the group having a BMI ≥30 kg/m² (43.4%, vs. 28.3%, p < 0.01) due to an increased rate of local recurrences (33.3% vs. 18.5%, p < 0.01). The rate of groin and distant recurrences was similar between both groups (p > 0.05). Noteworthy, we observed a significantly shorter disease free survival (DSF) of the obese patients in univariate analysis (HR 1.362, 95%CI 1.093-1.696, p = 0.006). Even in multivariate Cox-regression analysis including age, ECOG, tumor stage, type of surgery, nodal invasion, tumor grade, and comorbidities patients with BMI ≥30 kg/m² had a significantly shorter DFS (HR 1.811, 95%CI 1.005-3.262, p = 0.048). Conclusions: In this first large study about the association between obesity and prognosis of vulvar cancer patients, we observed that a BMI ≥30kg/m² was associated with shorter DFS, mainly attributed to a higher risk for local recurrence.


2011 ◽  
Vol 26 (2) ◽  
pp. 108-116 ◽  
Author(s):  
Li Chen ◽  
Yan Shi ◽  
Cheng-ying Jiang ◽  
Li-xin Wei ◽  
Ya-li Lv ◽  
...  

Aims To evaluate the prognostic value of vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor-alpha (PDGFR-α) and beta (PDGFR-β) expression in patients with hepatocellular carcinoma (HCC). Methods The expression of PDGFR-α, PDGFR-β and VEGF in 63 HCC patients who underwent curative resection was examined by immunohistochemistry (IHC). The correlations between the expression of these biomarkers and the clinicopathological characteristics were analyzed. Patient survival was analyzed by univariate analysis and Cox proportional hazards model. Results Univariate survival analysis showed that PDGFR-α or PDGFR-β overexpression was of no prognostic significance in predicting disease-free survival (DFS) and overall survival (OS) (p>0.05), while VEGF overexpression and PDGFR-α/PDGFR-β/VEGF coexpression were significantly correlated with worse DFS and poorer OS in HCC patients (P<0.05). More importantly, PDGFR-α/PDGFR-β/VEGF coexpression was an independent prognostic marker for poor survival as indicated by multivariate Cox regression analysis (DFS, hazard ratio 3.122, p=0.001; OS, hazard ratio 4.260, p=0.000). Conclusions Coexpression of PDGFR-α, PDGFR-β and VEGF could be considered an independent prognostic biomarker for predicting DFS and OS in HCC patients. This result could be used to identify patients at a higher risk of tumor recurrence and poor prognosis, and help to select therapeutic schemes for the treatment of HCC.


2021 ◽  
Vol 20 ◽  
pp. 153303382110458
Author(s):  
Lin Zhou ◽  
Jing Wang ◽  
Shao-cheng Lyu ◽  
Li-chao Pan ◽  
Xian-jie Shi ◽  
...  

Background: This presented study was aimed to evaluate the diagnostic and prognostic value of PD-L1+Neutrophils (PD-L1+NEUT) and neutrophil to lymphocyte ratio (NLR) based on our previous experience of Foxp3+Treg in transplantation. Methods: the NLR cutoff value of 1.79 was used to include 136 cases from the 204 patients with hepatocellular carcinoma (HCC) confirmed by clinical pathology, which were divided into highly-moderately and poorly differentiated HCC groups. The expressions of PD-L1+NEUT and Foxp3+Treg in peripheral blood and cancer tissue were detected with flow cytometry, meanwhile, PD-L1 and Foxp3 expressed in carcinoma and para-carcinoma tissues were marked by immunohistochemistry. Survival rates, including overall survival and disease-free survival, were calculated by the Kaplan–Meier curve and evaluated with the log-rank test. Finally, Cox risk regression model was used to analyze the independent risk factors for prognostic survival. Results: The level of PD-L1+NEUT, Foxp3+Treg, and NLR in peripheral blood of patients with poorly differentiated HCC were significantly increased (all P < .001). Both PD-L1+NEUT and NLR were positively correlated with Foxp3+Treg ( r = 0.479, P = .0017; r = 0.58, P < .0001). The level of PD-L1+NEUT and Foxp3+Treg as well as PD-L1 and Foxp3 in cancer tissue and patients with poorly differentiated HCC were obviously increased (all P < .01), respectively. Cox regression analysis indicated that PD-L1+NEUT, NLR, and Foxp3+Treg were independent risk factors for the prognosis ( P = .000, .000, .006) with a RR and 95%CI of 2.704-(2.155-3.393), 3.139-(2.361-4.173), 1.409-(1.105-1.798), respectively. Conclusion: PD-L1+NEUT, NLR, and Foxp3+Treg are independent risk factors for prognosis which maybe new marker of lower survival benefits.


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